Mapping the Gene Causing Hereditary Primary Hyperparathyroidism in a Portuguese Kindred to Chromosome 1q22-q31

Abstract

A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPT Port . Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPT Port to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3.46-5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPT Port has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors. (J Bone Miner Res 1999;14:230-239)

Genetic analysis of the MEN1 gene and HPRT2 locus in two Italian kindreds with familial isolated hyperparathyroidism

“…, 1998a). Indeed, as usually observed in classical HPT‐JT cases, the parathyroid abnormality was characterized by a solitary adenoma with a cystic component, associated with loss of heterozygosity (LOH) at the HPRT2 locus (Williamson et al. , 1999).…”

Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism

“…The detailed characterisation of the syndromic forms of PHPT has helped to identify some of the genes and chromosomal regions that are involved in the tumourigenesis of FIHP. -5 II-1 F 50 Unaff -5 II-2 M 54 Uk -5 II-4 F 63 Aff ----wt 5 II-10 F 55 Aff 2.74 169 c 4187 d 1 Adenoma wt 5 III-1 F 26 Uk -5 III-2 F 23 Uk -5 III-3 F 20 Aff 3. A few large FIHP families have been associated with mutations in the MEN1 (12,13) or the calcium receptor (CaR ) genes (14), and some additional families have been assigned to the HPT-JT locus on the basis of linkage analysis (15,16). However, for the vast majority of FIHP families, the genetic background remains unknown and the involvement of known candidate genes has been only partly evaluated (17,18).…”

“…However, for the vast majority of FIHP families, the genetic background remains unknown and the involvement of known candidate genes has been only partly evaluated (17,18). In the MEN1-related FIHP, the PHPT seems to run a milder course, with the occurrence of multiglandular disease or hyperplasia (12,13), and in the HPT-JT-related FIHP, solitary adenoma and even parathyroid carcinoma have been demonstrated (15,16), whereas in a single family with a CaR mutation the parathyroid lesions mainly consisted of moderate hyperplasia (14).…”

Familial and Hereditary Forms of Primary Hyperparathyroidism

“…CLINICAL ASPECTS OF PRIMARY HYPERPARATHYROIDISM Reproduced with permission from 126,128 . parathyroid carcinomas. [132][133][134][135] These distinctions may be helped by the identification of additional features, and a search for jaw tumors, renal, pancreatic, thyroid, and testicular abnormalities may help to identify HPT-JT patients. The jaw tumors in HPT-JT are different from the brown tumors observed in some patients with PHPT and do not resolve after parathyroidectomy.…”